This study examined the potential role of metabotropic glutamate receptors (mGluRs) in the dorsomedial hypothalamus (DMH) by assessing the cardiovascular effects of microinjecting the agonist trans-1-aminocyclopentane-1, 3- dicarboxylate (tACPD) into this region in urethan-anesthetized rats. Dose-related tachycardia was observed after unilateral microinjection of 1S 3R-tACPD (10-200 pmol/50nl) but not after injection of 1R, 3S-tACPD, which has been reported to have little or no activity at mGluRs. Microinjection of dihydroxyphenylglycine, an agonist at mGluRs linked to phosphoinositide hydrolysis, resulted in increases in heart rate that correlated closely in magnitude to those seen after injection of the same dose of 1S, 3R-tACPD. Coinjection of the N-methyl-D-aspartate (NMDA) receptor antagonist DL-2- amino-5-phosphonopentanoic acid, given at doses shown to elicit selective blockade of NMDA ionotropic glutamate receptors, reduced the increase in heart rate evoked by 100 pmol 1S, 3R-tACPD alone. Thus the DMH contains functional mGluRs, and stimulation of these receptors activates the same sympathoexcitatory mechanism characterized previously to provoke dose-related tachycardia.